The pH-dependent effect of cationic and non-ionic delmopinol on planktonic and biofilm bacteria

Objectives: The primary purpose was to evaluate the antimicrobial effects of cationic and non-ionic delmopinol on planktonic and biofilm bacteria. Methods: Determination of the minimum inhibitory concentrations on planktonic and biofilm bacteria was performed below and above the plc-value of delmopinol. Test bacteria were Staphylococcus aureus, Staphylococcus epidermidis, Escherichia cod and Pseudomonas aeruginosa. Comparisons were made with three antimicrobial agents and "quaternary" delmopinol. Synergy testing of delmopinol was determined with serial dilutions of delmopinol with the other compounds in a checkerboard fashion, and the fractional inhibitory concentration index (FIC) was calculated. Results: Delmopinol showed minor differences between its MIC- and MBEC-values for all bacterial strains (MBEC/MIC-ratios of 1-2). For the other compounds the difference between their MIC- and MBEC-values were higher and varied considerably between the bacteria. The MIC- and MBEC-concentrations were lower at pH where the non-ionic form of delmopinol dominates. "Quaternary" delmopinol showed the same MIC-concentrations as delmopinol, but needed much higher concentrations to kill biofilm bacteria. Synergy testing showed FIC-indices of 0.5-1. Conclusions: The biofilm penetration of non-ionic delmopinol is better than for cationic delmopinol. Likewise, the cationic test reference samples exerted limited biofilm penetration. The increased efficacy of non-ionic delmopinol is probably due to reduced binding to negative groups in the extracellular matrix of polymeric substances surrounding biofilm bacteria. It is also proposed that the non-ionised form of delmopinol deposits on the biofilm surface. Higher amounts of delmopinol than expected will therefore accumulate. Combinations of delmopinol with other compounds suggests an additive antimicrobial effect

Reduced Use of Antibiotics and Nasal Decongestants During Treatment with a Mouthwash Containing Delmopinol.

PURPOSE: To evaluate the use of concomitant medication in combination with a mouthwash of delmopinol HCl 0.2% based on data from 8 phase III efficacy studies on the mouthwash. MATERIALS AND METHODS: Clinical data obtained from 8 previously performed phase III studies, carried out to document the clinical efficacy of a mouthwash of delmopinol HCl 0.2% with respect plaque and gingivitis, were used to analyse the use of concomitant medication. In these 8 randomised double-blind clinical phase III studies the patients were - in addition to their normal oral hygiene measures - treated for 2-6 months with mouthwashes containing delmopinol HCl 0.2%, delmopinol HCl 0.1%, chlorhexidine digluconate 0.2% or placebo. The number of visits in each study was three. Each time the patients visited the dentist for efficacy determinations, other data were also recorded. One of these was whether the patient had used any other medication during the study. In this paper, the number of treatments of different types of concomitant medication (antibiotics, nasal decongestants and others) was used as a basis for statistical comparisons between the different test groups. RESULTS: For antibiotics (all indications), a 27% lower number of treatments was obtained in the delmopinol 0.2% group in comparison with the placebo group, and a 41% decrease was observed for treatments with antibiotics for respiratory infections. For nasal decongestants, the number of treatments was 53% lower in the delmopinol 0.2% group. CONCLUSIONS: The delmopinol HCl 0.2% solution in patients with gingivitis provided a statistically significant reduction of concomitant use of antibiotics and nasal decongestants

Adsorption of delmopinol at the solid/liquid interface - the role of the acid-base equilibrium

Delmopinol is a tertiary amine surfactant that is used to counteract dental plaque formation. As it is of interest to understand the interfacial behavior from both fundamental and applied perspectives the adsorption of delmopinol to model surfaces was investigated. Adsorption on Teflon, titanium and stainless steel was studied by radioactive labeling and adsorption on silica was studied by quartz crystal microbalance (QCM), ellipsometry and particle electrophoresis. It was shown that the adsorption of delmopinol was complex and strongly influenced by pH and concentration. Pronounced peak values were detected in the adsorption curves (adsorbed amount versus concentration) exceeding the expected value for a bilayer type of structure. To account for this behavior two surface active component were assumed to be present. Accordingly, the high amounts result from the deposition of the component with lower solubility and the decrease at the critical micelle concentration can be explained by solubilization of this component. Based on data from several experimental methods and the pH dependence of the effect we propose an explanation in which the protonated and non-protonated forms of delmopinol represent the two components. However, it cannot be excluded that the component with the lower solubility could be a compound chemically different from delmopinol in the sample

The effect of delmopinol and fluoride on acid adaptation and acid production in dental plaque biofilms

OBJECTIVE: To investigate the effect of delmopinol and fluoride alone or in combination on acid adaptation and acid production in plaque biofilm bacteria in vitro. DESIGN: The effect of delmopinol and fluoride on acid adaptation was tested by exposing the biofilm bacteria, grown in a mini-flow cell system under static conditions, to pH 5.5 overnight in the presence of 0.16 mM delmopinol, 1 mF NaF or a combination of both. The following day, acid adaptation was evaluated by exposing the cells to an acid challenge for 2h at a pH known to kill non-adapted cells (pH 2.5). The cells were stained using LIVE/DEAD BacLight Viability stain and the number of viable (acid tolerant) cells was determined using confocal scanning laser microscopy. Control cells were treated in the same manner but without the exposure to delmopinol or fluoride. How delmopinol and fluoride affected acid production was assessed by measuring the pH-drop after glucose pulsing in the presence of delmopinol and/or different concentrations of fluoride. RESULTS: Fluoride alone or in combination with delmopinol affected the acid adaptation and significantly reduced the acid tolerance of the plaque biofilm. This effect was more pronounced when the two compounds were combined. Delmopinol alone did not affect acid adaptation. A combination of delmopinol and fluoride also reduced acid production at concentrations where neither of the compounds in isolation had an effect. CONCLUSION: Fluoride and delmopinol can work synergistically to affect acid adaptation and acid production in plaque biofilm bacteria

A clinical and microbiological study on the enantiomers of delmopinol

Objective The clinical part of this study aimed to investigate whether the racemate of delmopinol [(+/-)-delmopinol] is equivalent to its two enantiomers [(+)-delmopinol and (-)-delmopinol] with respect to efficiency and to determine and compare their pharmacokinetic properties. The purpose of the pre-clinical part was to elucidate possible differences in antimicrobial efficiency. Materials and methods The compounds were tested clinically in a double-blind, randomized, cross-over study comprising three treatment periods of 4 days each. The antimicrobial efficacy of the enantiomers was compared in vitro with respect to planktonic and biofilm bacteria of different species. Results No statistically significant differences in prevention of plaque formation were observed. Except for a somewhat higher systemic exposure in terms of AUC and C-max indicated for (-)-delmopinol compared to (+)-delmopinol, the pharmacokinetic properties were similar. The most common adverse event was a transient anaesthetic feeling in the mouth. This event was reported with the same frequency for all three test solutions. The enantiomers showed similar antimicrobial effects on planktonic bacteria and their biofilms. Conclusions The enantiomers were found to be equally effective with respect to inhibition of plaque development and only minor differences were observed with respect to their pharmacokinetic properties. No differences could be observed in the adverse events reports. There is, therefore, no reason to use one of the enantiomers of delmopinol instead of the racemate. This was further supported by the antimicrobial tests. It is suggested that the combined action of cationic and neutral delmopinol is important for its effect on biofilms

Delmopinol - adsorption to and absorption through the oral mucosa

The findings indicate that delmopinol interacts with the salivary film of the upper labial mucosa and affects its polarity. It appears that delmopinol assists in the maintenance of the hydrophilicity of the mucosal pellicle and thereby also reinforcing hydration of the mucosa. The rat autoradiograms, showed that radioactivity remains in the oral mucosa after 24 h, but diffuses through the mucosal membranes into the systemic circulation

Microbial community response to growing season and plant nutrient optimisation in a boreal Norway spruce forest

Interactions between Norway spruce trees and bacteria and fungi in nutrient limited boreal forests can be beneficial for tree growth and fitness. Tree-level effects of anthropogenic nutrient addition have been well studied, however understanding of the long-term effects on the associated microbiota is limited. Here, we report on the sensitivity of microbial community composition to the growing season and nutrient additions. Highthroughput sequencing of the bacterial 16S rRNA gene and fungal ITS1 region was used to characterise changes in the microbial community after application of a complete mineral nutrient mixture for five and 25 years. The experiment was conducted using the Flakaliden forest research site in northern boreal Sweden and included naturally low nutrient control plots. Needle and fine root samples of Norway spruce were sampled in addition to bulk soil during one growing season to provide comprehensive insight into phyllosphere and belowground microbiota community changes. The phyllosphere microbiota was compositionally distinct from the belowground communities and phyllosphere diversity increased significantly over the growing season but was not influenced by the improved nutrient status of the trees. In both root and soil samples, alpha diversity of fungal, in particular ectomycorrhizal fungi (EMF), and bacterial communities increased after long-term nutrient optimisation, and with increasing years of treatment the composition of the fungal and bacterial communities changed toward a community with a higher relative abundance of nitrophilic EMF and bacterial species but did not cause complete loss of nitrophobic species from the ecosystem. From this, we conclude that 25 years of continuous nutrient addition to a boreal spruce stand increased phylotype richness and diversity of the microbiota in the soil, and at the root-soil interface, suggesting that long-term anthropogenic nutrient inputs can have positive effects on belowground biodiversity that may enhance ecosystem robustness. Future studies are needed to assess the impact of these changes to the microbiota on ecosystem carbon storage and nitrogen cycling in boreal forests.Bio4Energ